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Open data
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Basic information
Entry | Database: PDB / ID: 8hgp | ||||||
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Title | The EREG-bound EGFR/HER2 ectodomain complex | ||||||
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![]() | MEMBRANE PROTEIN | ||||||
Function / homology | ![]() luteinizing hormone signaling pathway / ovarian cumulus expansion / ovulation / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus ...luteinizing hormone signaling pathway / ovarian cumulus expansion / ovulation / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / primary follicle stage / female meiotic nuclear division / PI3K events in ERBB4 signaling / regulation of microtubule-based process / ErbB-3 class receptor binding / positive regulation of innate immune response / semaphorin receptor complex / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / neurotransmitter receptor localization to postsynaptic specialization membrane / response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / oocyte maturation / diterpenoid metabolic process / mRNA transcription / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / midgut development / neuromuscular junction development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / epidermal growth factor receptor binding / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / positive regulation of Rho protein signal transduction / intracellular vesicle / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / enzyme-linked receptor protein signaling pathway / positive regulation of transcription by RNA polymerase I / Signaling by EGFR / response to cobalamin / ERBB2-ERBB3 signaling pathway / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / eyelid development in camera-type eye / oligodendrocyte differentiation / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / Respiratory syncytial virus (RSV) attachment and entry / semaphorin-plexin signaling pathway / regulation of JNK cascade / positive regulation of cell division / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / keratinocyte proliferation / positive regulation of cell adhesion / negative regulation of mitotic cell cycle / hair follicle development / SHC1 events in ERBB4 signaling / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / MAP kinase kinase kinase activity / positive regulation of protein targeting to membrane / positive regulation of protein kinase activity / embryonic placenta development / anatomical structure morphogenesis / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / regulation of angiogenesis / coreceptor activity / Schwann cell development / salivary gland morphogenesis Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.53 Å | ||||||
![]() | Zhang, Z. / Bai, X. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure and dynamics of the EGFR/HER2 heterodimer. Authors: Xue Bai / Pengyu Sun / Xinghao Wang / Changkun Long / Shuyun Liao / Song Dang / Shangshang Zhuang / Yongtao Du / Xinyi Zhang / Nan Li / Kangmin He / Zhe Zhang / ![]() Abstract: HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly ...HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 221.3 KB | Display | ![]() |
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PDB format | ![]() | 175.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 46.1 KB | Display | |
Data in CIF | ![]() | 66.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 34745MC ![]() 8hgoC ![]() 8hgsC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 2 types, 2 molecules BA
#1: Protein | Mass: 82149.758 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P04626, receptor protein-tyrosine kinase |
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#2: Protein | Mass: 81075.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P00533, receptor protein-tyrosine kinase |
-Protein/peptide , 1 types, 1 molecules C
#3: Protein/peptide | Mass: 5578.410 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Sugars , 3 types, 4 molecules ![](data/chem/img/NAG.gif)
#4: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Type: oligosaccharide / Mass: 748.682 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source |
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#5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#6: Sugar |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: EREG-bound EGFR/HER2 ectodomain complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.2 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 4.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60.8 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.53 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 273388 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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